ArticleThe American journal of pathology2009
IL-4/IL-13-dependent alternative activation of macrophages but not microglial cells is associated with uncontrolled cerebral cryptococcosis.
Article in The American journal of pathology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
59 citing papers in PubMed, 96 citations in OpenAlex.
- Oral Lipid Nanocrystal Amphotericin B for Cryptococcal Meningitis: A Randomized Clinical Trial.Clinical infectious diseases : an official publication of the Infectious Diseases Society of America · 2023Trial
- Early ART After Cryptococcal Meningitis Is Associated With Cerebrospinal Fluid Pleocytosis and Macrophage Activation in a Multisite Randomized Trial.The Journal of infectious diseases · 2015Trial
- Cerebrospinal fluid cytokine profiles predict risk of early mortality and immune reconstitution inflammatory syndrome in HIV-associated cryptococcal meningitis.PLoS pathogens · 2015Trial
- Immunoregulation in Fungal Infections: A Review and Update on the Critical Role of Myeloid-Derived Suppressor Cells.Journal of fungi (Basel, Switzerland) · 2025Review
- Innate Pulmonary Phagocytes and Their Interactions with PathogenicJournal of fungi (Basel, Switzerland) · 2023Review
- Alternatively activated lung alveolar and interstitial macrophages promote fungal growth.iScience · 2023Article
- Emerging and re-emerging fungal threats in Africa.Parasite immunology · 2023Review
- Cryptococcal Immune Reconstitution Inflammatory Syndrome: From Clinical Studies to Animal Experiments.Microorganisms · 2022Review
- Review
- Article
- Macrophages in Microbial Pathogenesis: Commonalities of Defense Evasion Mechanisms.Infection and immunity · 2022Review
- Fungal CNS Infections in Africa: The Neuroimmunology of Cryptococcal Meningitis.Frontiers in immunology · 2022Review
- A preliminary study on the characteristics of Th1/Th2 immune response in cerebrospinal fluid of AIDS patients with cryptococcal meningitis.BMC infectious diseases · 2021Article
- IL-4R alpha deficiency influences hippocampal-BDNF signaling pathway to impair reference memory.Scientific reports · 2020Article
- Monocytes and the Host Response to Fungal Pathogens.Frontiers in cellular and infection microbiology · 2020Review
- Group 2 Innate Lymphoid Cells (ILC2) Suppress Beneficial Type 1 Immune Responses During Pulmonary Cryptococcosis.Frontiers in immunology · 2020Article
- Cryptococcus neoformans and Cryptococcus gattii clinical isolates from Thailand display diverse phenotypic interactions with macrophages.Virulence · 2019Article
- Article
- Inflammatory monocytes are detrimental to the host immune response during acute infection with Cryptococcus neoformans.PLoS pathogens · 2019Article
- HIV-Associated Cryptococcal Meningitis Occurring at Relatively Higher CD4 Counts.The Journal of infectious diseases · 2019Article
Corrections and comments
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Authors and funding
8 authors at 5 institutions in 4 countries.
Funding
Abstract
Both interleukin (IL)-4- and IL-13-dependent Th2-mediated immune mechanisms exacerbate murine Cryptococcus neoformans-induced bronchopulmonary disease. To study the roles of IL-4 and IL-13 in cerebral cryptococcosis, IL-4 receptor alpha-deficient (IL-4Ralpha(-/-)), IL-4-deficient (IL-4(-/-)), IL-13-deficient (IL-13(-/-)), IL-13 transgenic (IL-13(T/+)), and wild-type mice were infected intranasally. IL-13(T/+) mice displayed a higher fungal brain burden than wild-type mice, whereas the brain burdens of IL-4Ralpha(-/-), IL-4(-/-), and IL-13(-/-) mice were significantly lower as compared with wild-type mice. On infection, 68% of wild-type mice and 88% of IL-13-overexpressing IL-13(T/+) mice developed significant cerebral lesions. In contrast, only a few IL-4Ralpha(-/-), IL-4(-/-), and IL-13(-/-) mice had small lesions in their brains. Furthermore, IL-13(T/+) mice harbored large pseudocystic lesions in the central nervous system parenchyma, bordered by voluminous foamy alternatively activated macrophages (aaMphs) that contained intracellular cryptococci, without significant microglial activation. In wild-type mice, aaMphs tightly bordered pseudocystic lesions as well, and these mice, in addition, showed microglial cell activation. Interestingly, in resistant IL-4(-/-), IL-13(-/-), and IL-4Ralpha(-/-) mice, no aaMphs were discernible. Microglial cells of all mouse genotypes neither internalized cryptococci nor expressed markers of alternative activation, although they displayed similar IL-4Ralpha expression levels as macrophages. These data provide the first evidence of the development of aaMphs in a central nervous system infectious disease model, pointing to distinct roles of macrophages versus microglial cells in the central nervous system immune response against C. neoformans.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.